HER2 is a member of the human epidermal growth factor receptor (HER/EGFR-
/ERBB) family. Amplification or over-expression of this oncogene has been shown to play a major
role in the development and progression of certain destructive types of breast cancer. Several
drugs like Trastuzumab, Pertuzumab, Capecitabine, and Letrozole are used in the patients with
metastatic breast cancer that overexpress the HER2 receptor. We aimed to investigate, the prevalence,
ADME prediction, biological activity prediction of novel HER2/ EGFR mutations in breast
cancer. Literature review shows that pyrano pyrimidin scaffold plays important role in the treatment
of Brest cancer. So we have to design novel 6,7-Dihydropyrano [2,3-d] pyrimidin-5-one derivatives
with virtual screening techniques. Molecular target prediction shows that all derivatives
act on tyrosine kinase. Among all the compounds H11 (-8.8 kcal/mol), H2 (-8.7 kcal/mol), H15
(-8.6 Kcal/mol), and H17 (-8.7 Kcal/mol) has a maximum binding affinity as compared to Cipecitabine
(-6.0 kcal/mol), STD1 (-7.2 Kcal/mol) and STD2 (-7.9 Kcal/mol) and other derivatives.
Most of the compounds are moderately active and do not cross the blood brain barrier. It's bioactivity
prediction shows that all compounds are active to moderately active. These positive results
show that it could be further investigated and explored.
Keywords: HER2, Trastuzumab, Capecitabine, EGFR, 6, 7-Dihydropyrano [2, 3-d] pyrimidin.
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